• at 3-6 months of age, the mean number of corpora lutea (CL) per mouse at estrus is reduced to 42.5% of CL number in control females

• at day 7 of gestation (early pregnancy), female homozygotes show a significant reduction in the mean number of active CL (52% of wild-type number), with no significant changes in serum progesterone concentrations

• when young female mutants are mated to control males, latency to first mating and age of the female at first mating are significantly delayed; however, maternal age at first conception is similar between groups (~6 weeks)

• male homozygotes fail to successfully impregnate control females until roughly 9 weeks of age; one mutant male failed to impregnate either of the females with whom he was caged for >90 days

• delayed attainment of fertility in males, but not females, is likely to contribute to the delayed age at first conception

• unlike prepubertal control females, mutant females fail to mate within 4 days of introduction of the male, no peak in mating activity is observed, and mean latency to first mating is delayed by ~10 days, suggesting altered pheromonal sensitivity and/or male-induced acceleration of female puberty
(J:79216)

• although puberty onset is delayed in female homozygotes, the age of attainment of fertility is similar between mutant and wild-type females
(J:79216)

• both puberty onset and attainment of fertility are delayed in male homozygotes
(J:79216)

• males homozygotes display a significant delay in the onset of puberty as shown by changes in testicular function, SV weight, germ cell formation, and timing of preputial separation
(J:105921)

• however, with time and repeated mating, mutant females are able to normalize their luteal response to sterile mating and display pseudopregnancies of comparable duration and frequency to that of wild-type controls

• at 3-6 months of age, the mean number of corpora lutea (CL) per mouse at estrus is reduced to 42.5% of CL number in control females

• at day 7 of gestation (early pregnancy), female homozygotes show a significant reduction in the mean number of active CL (52% of wild-type number), with no significant changes in serum progesterone concentrations

• at 3.5 months of age, the ratio between total bone mineral content to crown-rump length and total bone area to crown-rump length is reduced by 45% and 23%, respectively, in mutant versus control males
(J:105686)

• at 10 weeks after induction of diabetes with streptozotocin, female homozygotes develop levels of hyperglycemia that are equivalent to those observed in STZ-treated wild-type and heterozygous control mice; however, STZ-treated mutant females fail to show evidence of glomerulosclerosis, increases in glomerular volume or increases in the ratio of mesangial area to total glomerular area, indicating protection against diabetes-induced nephropathy

• in the inhibitory avoidance learning task (a measure of cognitive aging), learning and memory retention in old homozygotes (24-30 months of age) does not decline between the 24-hr, 7-day and 28-day retention tests and is not significantly different from that in young homozygotes (2-4 months of age)

• differences in retention are not attributed to altered locomotor behavior or emotionality, as between the ages of 17 and 20 months wild-type and mutant mice do not differ in number of open or closed arms entered, time spent in closed or open arms or time taken to first enter an open arm in the elevated-plus maze test

• following intracerebroventricular (ICV) ghrelin injection, both fasted and fed male homozygotes show a blunted feeding response relative to similarly-treated control males

• ICV injection of ghrelin generated a similar increase in total serum gherlin levels in mutant and control males (4.9- and 6.4-fold, respectively); however, ghrelin had no acute effect on serum leptin or corticosterone levels in either group of mice

• at 4-5 months of age, plasma glucose levels in ad libitum-fed homozygotes (male and females) are lower than in control mice in measurements taken in both morning and afternoon; however, these reductions are sex-dependent

• plasma glucose levels in fed young adult homozygotes sacrificed in the morning are significantly reduced in males, but are nonsignificantly lower in female homozygotes relative to control mice

• although morning plasma glucose levels are normal in fed female homozygotes, they drop significantly in the afternoon, suggesting a different diurnal pattern of glucose regulation in females than males

• at 4-5 months of age, basal (unstressed) plasma corticosterone levels in female homozygotes are similar to those in control females, while mutant males display significantly elevated levels over control males in the afternoon only

• following repeated anesthesia and exposure to a novel cage, corticosterone levels in stressed female homozygotes are similar to those in stressed control females

• insulin tolerance tests performed in 7-mo-old homozygotes of both sexes in the random fed state indicate a further reduction in blood glucose levels of 60% and 67% at 40 and 60 min relative to wild-type levels